Reprogramming of mouse somatic cells into pluripotent stem-like cells using a combination of small molecules

Phil Jun Kang, Jai Hee Moon, Byung Sun Yoon, Solji Hyeon, Eun Kyoung Jun, Gyuman Park, Wonjin Yun, Jiyong Park, Minji Park, Aeree Kim, Kwang Youn Whang, Gou Young Koh, Sejong Oh, Seungkwon You

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Somatic cells can be reprogrammed to generate induced pluripotent stem cells (iPSCs) by overexpression of four transcription factors, Oct4, Klf4, Sox2, and c-Myc. However, exogenous expression of pluripotency factors raised concerns for clinical applications. Here, we show that iPS-like cells (iPSLCs) were generated from mouse somatic cells in two steps with small molecule compounds. In the first step, stable intermediate cells were generated from mouse astrocytes by Bmi1. These cells called induced epiblast stem cell (EpiSC)-like cells (iEpiSCLCs) are similar to EpiSCs in terms of expression of specific markers, epigenetic state, and ability to differentiate into three germ layers. In the second step, treatment with MEK/ERK and GSK3 pathway inhibitors in the presence of leukemia inhibitory factor resulted in conversion of iEpiSCLCs into iPSLCs that were similar to mESCs, suggesting that Bmi1 is sufficient to reprogram astrocytes to partially reprogrammed pluripotency. Next, Bmi1 function was replaced with Shh activators (oxysterol and purmorphamine), which demonstrating that combinations of small molecules can compensate for reprogramming factors and are sufficient to directly reprogram mouse somatic cells into iPSLCs. The chemically induced pluripotent stem cell-like cells (ciPSLCs) showed similar gene expression profiles, epigenetic status, and differentiation potentials to mESCs.

Original languageEnglish
Pages (from-to)7336-7345
Number of pages10
JournalBiomaterials
Volume35
Issue number26
DOIs
Publication statusPublished - 2014 Jan 1

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Pluripotent Stem Cells
Stem cells
Molecules
Germ Layers
Leukemia Inhibitory Factor
Transcription factors
Mitogen-Activated Protein Kinase Kinases
Gene expression
Induced Pluripotent Stem Cells
Transcription Factors
Epigenomics
Astrocytes
Stem Cells
MAP Kinase Signaling System
Transcriptome

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Reprogramming of mouse somatic cells into pluripotent stem-like cells using a combination of small molecules. / Kang, Phil Jun; Moon, Jai Hee; Yoon, Byung Sun; Hyeon, Solji; Jun, Eun Kyoung; Park, Gyuman; Yun, Wonjin; Park, Jiyong; Park, Minji; Kim, Aeree; Whang, Kwang Youn; Koh, Gou Young; Oh, Sejong; You, Seungkwon.

In: Biomaterials, Vol. 35, No. 26, 01.01.2014, p. 7336-7345.

Research output: Contribution to journalArticle

Kang, PJ, Moon, JH, Yoon, BS, Hyeon, S, Jun, EK, Park, G, Yun, W, Park, J, Park, M, Kim, A, Whang, KY, Koh, GY, Oh, S & You, S 2014, 'Reprogramming of mouse somatic cells into pluripotent stem-like cells using a combination of small molecules', Biomaterials, vol. 35, no. 26, pp. 7336-7345. https://doi.org/10.1016/j.biomaterials.2014.05.015
Kang, Phil Jun ; Moon, Jai Hee ; Yoon, Byung Sun ; Hyeon, Solji ; Jun, Eun Kyoung ; Park, Gyuman ; Yun, Wonjin ; Park, Jiyong ; Park, Minji ; Kim, Aeree ; Whang, Kwang Youn ; Koh, Gou Young ; Oh, Sejong ; You, Seungkwon. / Reprogramming of mouse somatic cells into pluripotent stem-like cells using a combination of small molecules. In: Biomaterials. 2014 ; Vol. 35, No. 26. pp. 7336-7345.
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